Plicamycin

Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. It is an RNA synthesis inhibitor.[1] The manufacturer discontinued production in 2000. Several different structures are currently reported in different places all with the same chromomycin core, but with different stereochemistry in the glycoside chain, a 1999 study has re-investigated the compound and proposed a revised structure.[2]

Plicamycin
Clinical data
Other namesAureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
AHFS/Drugs.comMicromedex Detailed Consumer Information
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
  • (1S)-5-deoxy-1-C-((2S,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-arabino-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1→3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1→3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl)-1-O-methyl-D-xylulose
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.162.065
Chemical and physical data
FormulaC52H76O24
Molar mass1085.156 g·mol−1
3D model (JSmol)
  • CO[C@H](C(=O)[C@@H](O)[C@@H](C)O)C1Cc2cc3cc(O[C@H]4C[C@@H](O[C@H]5C[C@@H](O)[C@H](O)[C@@H](C)O5)[C@@H](O)[C@@H](C)O4)c(C)c(O)c3c(O)c2C(=O)[C@H]1O[C@H]1C[C@@H](O[C@H]2C[C@@H](O[C@H]3C[C@](C)(O)[C@H](O)[C@@H](C)O3)[C@H](O)[C@@H](C)O2)[C@H](O)[C@@H](C)O1
  • InChI=1S/C52H76O24/c1-18-29(72-34-14-30(43(58)21(4)68-34)73-33-13-28(54)42(57)20(3)67-33)12-26-10-25-11-27(49(66-9)48(63)41(56)19(2)53)50(47(62)39(25)46(61)38(26)40(18)55)76-36-16-31(44(59)23(6)70-36)74-35-15-32(45(60)22(5)69-35)75-37-17-52(8,65)51(64)24(7)71-37/h10,12,19-24,27-28,30-37,41-45,49-51,53-61,64-65H,11,13-17H2,1-9H3/t19-,20-,21-,22-,23-,24-,27?,28-,30-,31-,32-,33+,34+,35+,36+,37+,41+,42-,43+,44-,45-,49+,50+,51-,52+/m1/s1 checkY
  • Key:CFCUWKMKBJTWLW-GWRQQDNDSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Uses

Plicamycin has been used in the treatment of testicular cancer,[3][4] Paget's disease of bone,[5][6] and, rarely, the management of hypercalcemia.

Plicamycin has been tested in chronic myeloid leukemia.[7]

Plicamycin is currently used in multiple areas of research, including cancer cell apoptosis[8] and as a metastasis inhibitor.[9]

One elucidated pathway shows it interacts by cross-binding chromatin GC-rich promoter motifs, thereby inhibiting gene transcription.[10]

References
  1. "Mithramycin A". Fermentek.
  2. Wohlert SE, Künzel E, Machinek R, Méndez C, Salas JA, Rohr J (January 1999). "The structure of mithramycin reinvestigated". Journal of Natural Products. 62 (1): 119–121. doi:10.1021/np980355k. PMID 9917296.
  3. Kennedy BJ, Torkelson JL (May 1995). "Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin)". Medical and Pediatric Oncology. 24 (5): 327–328. doi:10.1002/mpo.2950240511. PMID 7700186.
  4. Brown JH, Kennedy BJ (January 1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". The New England Journal of Medicine. 272 (3): 111–118. doi:10.1056/NEJM196501212720301. PMID 14224214.
  5. Hall TJ, Schaeublin M, Chambers TJ (September 1993). "The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro". Biochemical and Biophysical Research Communications. 195 (3): 1245–1253. doi:10.1006/bbrc.1993.2178. PMID 8216256.
  6. Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV, Rohr J (July 2003). "Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target". Biochemistry. 42 (27): 8313–8324. doi:10.1021/bi034091z. PMID 12846580.
  7. Dutcher JP, Coletti D, Paietta E, Wiernik PH (May 1997). "A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia". Leukemia Research. 21 (5): 375–380. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.
  8. Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK (November 2006). "Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites". Molecular Cancer Therapeutics. 5 (11): 2737–2746. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.
  9. Lin RK, Hsu CH, Wang YC (November 2007). "Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells". Anti-Cancer Drugs. 18 (10): 1157–1164. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.
  10. Majee S, Chakrabarti A (May 1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology. 57 (9): 981–987. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.
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